作者
Richard W Tsika, Christine Schramm, Gretchen Simmer, Daniel P Fitzsimons, Richard L Moss, Juan Ji
发表日期
2008/12/26
期刊
Journal of Biological Chemistry
卷号
283
期号
52
页码范围
36154-36167
出版商
Elsevier
简介
TEA domain (TEAD) transcription factors serve important functional roles during embryonic development and in striated muscle gene expression. Our previous work has implicated a role for TEAD-1 in the fast-to-slow fiber-type transition in response to mechanical overload. To investigate whether TEAD-1 is a modulator of slow muscle gene expression in vivo, we developed transgenic mice expressing hemagglutinin (HA)-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that striated muscle-restricted HA-TEAD-1 expression induced a transition toward a slow muscle contractile protein phenotype, slower shortening velocity (Vmax), and longer contraction and relaxation times in adult fast twitch extensor digitalis longus muscle. Notably, HA-TEAD-1 overexpression resulted in an unexpected activation of GSK-3α/β and decreased nuclear β-catenin and NFATc1/c3 protein. These effects …
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